Booster Vaccination against Yellow Fever in Gambian children-(BoVY) -a Phase 3 clinical trial to establish safety and immunogenicity of repeated YF vaccination in healthy Gambian children of different ages.

Background: Yellow fever (YF) is a mosquito-borne and recently re-emerging viral haemorrhagic fever endemic to sub-Saharan Africa and South America. A highly effective vaccine against YF is licensed and recommended as part of routine childhood immunisation as a single dose at 9 months. Recent observational data demonstrate waning immunity following single primary vaccination and suggest that children in endemic areas may require booster vaccination. Methods: This open-label, non-randomised clinical vaccine trial (ClinicalTrials.gov, NCT05332197, registered on 31 March 2022, URL: https://clinicaltrials.gov/study/NCT05332197) will assess the safety and immunogenicity of a booster dose of the licensed 17D YF vaccine in Gambian children. The trial will recruit 750 children in three cohorts of different ages (250 each). All children were vaccinated with the 17D YF vaccine at 9-10 months of age as part of clinical trials run by the Medical Research Council (MRC) Unit The Gambia, and are thus well-characterised, including basic clinical, anthropometric, and post-primary immunogenicity data. The children will receive booster doses at 15 months, 4 years, or 8.5 years. Serum samples will be taken before and 28 days after the booster, with additional sampling for exploratory endpoints in subgroups. Adverse events are solicited for the first three days following vaccination and recorded throughout the study period. The primary objective of the trial is to describe the safety and immunogenicity of the booster in the different age cohorts. Secondary objectives are to characterise the rate of sero-reversion (change from seropositive to seronegative) over a period of 9 months to 8 years following single primary vaccination and to profile the immune response to the booster to explore underlying mechanisms for the longevity of vaccine-induced antibody. Discussion: The results of this trial are likely to directly impact WHO recommendations on whether booster vaccination is required for children in endemic areas, and if so, the optimal timing of such a booster.